Aquaculture remains an important source of food, nutrition, income and livelihoods for millions of people around the world. In Cameroon, like in most Sub-Saharan African countries, natural breeding and traditional fishing occur in virtually every river, lake and pond and the aquaculture sector predominantly comprises of small-scale producers with some larger-scale commercial activities. Although so many Cameroonian natives are involved in aquaculture, little profit is realized from their activities. Barriers to fish production include insufficient quality and quantity of fingerlings, inadequate quality of feed, inadequate financing and weak technical capacities. These problems lead to a core challenge of low supply of fish, coupled with low returns to fish farming and marketing. The study therefore sought to determine the level of profitability of fish farming and assess the main determinants of profitability of fish farming. It used data collected from 60 fish farmers in the Fako Division of Cameroon through personal interviews, using a pre-tested questionnaire. The study adopted net profit analysis to determine profitability and a Cobb-Douglas power function to quantify the effects of various factors on profit. The study found that fish farming is a profitable business with a mean net profit of 1 896 443 FCFA per production cycle of 4 months. Linear regression revealed that profitability of fish farmers was influenced by the price of feed, price of fingerlings and the cost of labor. The implications of the findings are that profitability can be enhanced by building the capacity of fish farmers on how to make fish production and marketing more cost effective. Farmers therefore need to know how to manage both variable and fixed costs in order to maximize profits.